Education

• Dr. rer. nat., University of Bremen, Germany, 1989
• M.S., University of Bremen, 1986

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Areas of Interest

Nucleosides for anticancer, antiviral, and antibiotic therapies

Nucleoside antimetabolites such as gemcitabine, cytarabine, cladribine, fludarabine, clofarabine, acyclovir, ganciclovir, brivudine, zidovudine, stavudine, and emtricitabine are prodrugs that are widely used as anticancer agents or antiviral agents and their importance continues to increase. These antimetabolites utilize nucleoside salvage pathways for their transformation into active nucleoside triphosphates. Irrespective of the final intracellular targets of the triphosphates, which primarily are human or viral DNA and their respective polymerases or reverse transcriptases, the rate-limiting key activation step of the prodrugs is usually the initial conversion of the nucleoside to the corresponding monophosphate by phosphorylating enzymes, often deoxynucleoside kinases. Thymidine kinase (TK) is one of these deoxynucleoside kinases. Most eukaryotes and prokaryotes and many DNA viruses code for proteins with thymidine kinase activity. However, among all approved nucleoside antimetabolites only the HIV prodrugs zidovudine and stavudine are activated by human thymidine kinase 1 (hTK1). This is probably due to the fact that TKs have the most stringent substrate specificity among all nucleoside kinases and that crystal structures for drug design have only become available very recently. Dr. Tjarks’ research activities focus on the in silico design, synthesis, and biological evaluation of inhibitors and substrates of TKs from e.g. Bacillus anthracis and Epstein-Barr virus as well as from hTK1 for antibiotic, antiviral, and anticancer therapies.

A second research focus of Dr. Tjarks’ group is the synthesis of boron and lanthanide containing porphyrin-type macrocycles, which could be considered as “multipurpose” anticancer diagnostics and therapeutics. Due to their unique intrinsic properties boron/lanthanide containing porphyrin-type macrocycles could serve as MRI contrast agents, near-infrared imaging agents, neutron capture therapy (NCT) agents, radiationsensitizer, photosensitizer, and cancer chemotherapeutics.

A third research focus of Dr. Tjarks' group is the synthesis of boron and gadolinium containing compounds that are utilized for the construction of tumor-targeted liposomes and nanoparticles for Neutron Capture Therapy of Cancer. Targeted cellular receptors include the vascular endothelial growth factor receptor (VEGFR), the epithelial growth factor receptor (EGFR), and the folate receptor (FR).

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Publications

• Yang,W.,  Barth, R.F., Wu, G., Tjarks, W., Binns, P.  Riley, K. Boron neutron capture therapy of EGFR or EGFRvIII positive gliomas using either boronated monoclonal antibodies or epidermal growth factor as molecular targeting agents. Applied Radiation and Isotopes, 67,  S328-S331, 2009.
• Tiwari, T.; Mahasenan; K.; Pavlovicz; R.; Li, C.; Tjarks, W.; Carborane Clusters in Computational Drug Design: A Comparative Docking Evaluation using AutoDock, FlexX, Glide and Surflex; J. Chem. Inf. Model. 49,  1581-1589, 2009.
• Yang, W.; Barth, R. F.; Wu, W.; Huo, T.; Tjarks, W.; Ciesielski, M.;  Fenstermaker; R. A.;  Ross; B. D.;  Wikstrand; C. J.; Riley; K. J.;  Binns, P. J.; Convection enhanced delivery of boronated EGF as a molecular targeting agent for neutron capture therapy of brain tumors. J. Neurooncol. 95:355–365, 2009.
• Chandra, S.;  Tjarks, W.; Lorey, D.R., II, Barth, R. F. Quantitative subcellular imaging of boron from BNCT agents in individual mitotic and interphase human glioblastoma cells with SIMS. J. Microsc. 229, 92–103, 2008.
• Yang, Y.; Wu, G.; Barth, R.F.; Swindall, M.R.; Bandyopadhyaya, A.K.;  Tjarks, W.; Tordoff, K.; Moeschberger, M.; Sferra, T.J.; Binns, P.J.; Riley, K.J.; Ciesielski, M.J.; Fenstermaker, R.A.;  Wikstrand. C.J., Molecular targeting and treatment of composite EGFR wildtype and EGFRIIIgliomas using boronated monoclonal antibiodies; Clin. Cancer Res., 14,  883-91, 2008.
• Byun, Y.; Vogel, S.R.; Phipps, A.J.; Carnrot, C.; Eriksson, S.; Tiwari, R.; Tjarks, W.; Synthesis and biological evaluation of inhibitors of thymidine monophosphate kinase from Bacillus Anthracis. Nucleosides, Nucleotides, and Nucleic Acids, 27, 244-260, 2008.
• Barth, R.F.; Yang, W.; Wu, G.; Swindall, M.; Byun, Y.; Narayanasamy, S.; Tjarks, W.; Tordoff, K.; Moeschberger, M.L.; Eriksson, S.; Binns, P. J.; Riley, K. J.   Thymidine kinase 1 as a molecular target for boron neutron capture therapy of brain tumors.    Proc. Nat. Acad. Sci. U.S. 105,  17493-17497, 2008.

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Courses Taught

• Pharmacy 410: Introduction to Medicinal Chemistry (team-taught course).
• Pharmacy 605: Drug-receptor/enzyme interactions, drug design concepts, acidity and basicity of drugs, physicochemical properties and metabolism of drugs. Chemical and biochemical principles governing the properties of drugs. Drug categories include:  Analgesics, anesthetics, CNS depressants, CNS stimulants, cholinergics, adrenergics, and drugs for the treatment of neurodegenerative diseases.
• Pharmacy 606 : Chemical and biochemical principles governing the properties of drugs. Drug categories include: Antihypertensives,  antianginal, antiarrhythmics, anticoagulants, agents for congestive heart failure, antihistamines and antidiabetics (team-taught course).
• Pharmacy 607: Chemical and biochemical principles governing the properties of drugs. Drug categories include: Steroid hormones such as androgens, antiandrogens, estrogen and antiestrogens, adrenocorticoids, prostaglandins and NSAIDs agents, anticancer agents and antiviral agents. (team-taught course).
• Pharmacy 735: A study of the discovery and design of new drugs; topics include natural products isolation, molecular modeling, molecular targets, and biosynthesis and metabolism (team-taught course).
• Pharmacy 807: Targeted drug delivery systems for cancer and leukemia (team-taught course).
• Pharmacy 836: Selected topics in medicinal chemistry, the subject matter being drawn from the current literature (team-taught course).
• Pharmacy 837: Discovery, development, and mechanisms of action of drugs used to treat bacterial, fungal, viral, and parasitic infections (team-taught course).
• Pharmacy 852:  Introduction to Pharmaceutical Sciences, the profession of pharmacy, the College of Pharmacy and responsible research practices (team-taught course).
• Recipient of the 2009 Miriam R. Balshone Memorial Award For Distinguished Teaching in the Pharm. D. Program of The Ohio State University

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Professional Experience

• 2007-present: Associate Professor, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH
• 2001-2007: Assistant Professor, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH
• 2000-2001: Adjunct Assistant Professor, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH
• 1997-2001: Research Scientist, Division of Medicinal Chemistry & Pharmacognosy,
  College of Pharmacy, The Ohio State University, Columbus, OH
• 1994-1996: Research Associate, Department of Organic Chemistry, Uppsala University, Sweden
• 1990-1993: Postdoctoral Researcher, Division of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH
• 1986-1990: Research Associate, Department of Chemistry & Biology, University of Bremen, Germany

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